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Natural Science 2012年第12期4卷 1165-1178页

作者： roger S. Holmes Laura A. cox Department of Genetics and Southwest National Primate Research Center Texas Biomedical Research Institute San Antonio USA

Lipase I (enzyme name LIPI or LPDL) (gene name LIPI [human] or Lipi [mouse]) is a phospholipase which generates 2-acyl lysophosphatidic acid (LPA), a lipid mediator required for maintaining homeostasis of diverse biological functions and in activating cell surface recaptors. Bioinformatic methods were used to predict the amino acid sequences, secondary and tertiary structures and gene locations for LIPI genes and encoded proteins using data from several mammalian genome projects. LIPI is located on human chromosome 21 and is distinct from other phospholipase A1-like genes (LIPH and PS-PLA1). Mammalian LIPI genes contained 10 (human) or 11 (mouse) coding exons transcribed predominantly on the negative DNA strand. Mammalian LIPI protein subunits shared 61% - 99% sequence identities and exhibited sequence alignments and identities for key LIPI amino acid residues as well as extensive conservation of predicted secondary and tertiary structures with those previously reported for pancreatic lipase (PL), with “N-signal peptide”, “lipase” and “plat” structural domains. Comparative studies of mammalian LIPI sequences with LIPH, PS-PLA1 and pancreatic lipase (PL) confirmed predictions for LIPI N-terminal signal peptides (residues 1 - 15);predominantly conserved mammalian LIPI N-glycosylation sites (63NNSL and 396NISS for human LIPI);active site “triad” residues (Ser159;Asp183;His253);disulfide bond residues (238 - 251;275 - 286;289 - 297;436 - 455);and a 12 residue “active site lid”, which is shorter than for other lipases examined. Phylogenetic analyses supported a hypothesis that LIPI arose from a vertebrate LIPH gene duplication event within a mammalian common ancestral genome. In addition, LIPI, LIPH and PL-PLA1 genes were distinct from the vascular lipase (LIPG, LIPC and LPL) and pancreatic lipase (PL) gene families.

关键词： Mammalian LIPI Genes and Proteins Amino Acid Sequence Lipase I Evolution Phylogeny

Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study

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World Journal of Gastroenterology 2016年第16期22卷 4191-4200页

作者： I Jane cox Abil E Aliev Mary ME Crossey Mahvish Dawood Mamun Al-Mahtab Sheikh M Akbar Salimur Rahman Antonio Riva roger Williams Simon D Taylor-Robinson Institute of Hepatology London Foundation for Liver Research Department of Chemistry University College London Division of Digestive Diseases Department of Surgery and Cancer Imperial College London Department of Hepatology Bangabandhu Sheikh Mujib Medical University Department of Medical Sciences Toshiba General Hospital

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and ***: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLS-DA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance (ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the Mann-Whitney U test was used to compare metabolite levels depending on hepatitis B e-antigen (HBeAg) status and treatment with anti-viral therapy. A Benjamini-Hochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < ***: There were significant differences in age (P < 0.001), weight (P < 0.001), and body mass index (P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase (ALT) was significantly higher in the HCC group compared to controls (P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group (P = 0.004). A three-factor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgr

关键词： Urinary metabolic profiling Hepatocellular carcinoma Nuclear magnetic resonance spectroscopy Hepatitis B Bangladesh

The association of cardiovascular mortality with a first-degree family member history of different cardiovascular diseases

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Journal of Geriatric Cardiology 2021年第10期18卷 816-824页

作者： Charbel Gharios Mireille Leblebjian Samia Mora roger S.Blumenthal Miran A.Jaffa Marwan M.Refaat Department of Internal Medicine Division of CardiologyAmerican University of Beirut Medical CenterBeirutLebanon Cardiovascular Imaging Research Center Massachusetts General Hospital and Harvard Medical SchoolBostonMAUSA Epidemiology and Population Health Department Faculty of Health SciencesAmerican University of BeirutBeirutLebanon Center for Lipid Metabolomics Divisions of Preventive and Cardiovascular MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonMAUSA The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease BaltimoreMDUSA Department of Biochemistry and Molecular Genetics American University of Beirut Faculty of MedicineBeirutLebanon

OBJECTIVE To investigate which history of cardiovascular disease[coronary heart disease(CHD),stroke,or peripheral arterial disease]in a first-degree family member predicts cardiovascular *** We studied a prospective cohort(the Lipid Research Clinics Prevalence Study)from ten primary care centers across North *** primary outcome was cardiovascular mortality,assessed using cox survival *** There were 8,646 participants(mean age:47.4±12.1 years,46%women,52%of participants with hyperlipidemia)who were followed up for a mean duration of 19.4±4.9 *** were 1,851 deaths(21%),including 852 cardiovascular deaths.A paternal,maternal or sibling history of premature CHD(before 60 years)was present in 26%of participants,of stroke in 27%of participants,and of peripheral arterial disease in 24%of *** adjusting for risk factors(age,sex,systolic blood pressure,diastolic blood pressure,body mass index,smoking,fasting glucose,low-density lipoprotein cholesterol and triglycerides),only a paternal history of premature or any CHD,a maternal history of diabetes mellitus or premature or any CHD,and a sibling history of premature CHD,hypertension,or hyperlipidemia were individually predictive of cardiovascular *** adjusting for risk factors and the mentioned familial factors,only paternal and maternal histories of CHD,espe-cially before 60 years,remained predictive of cardiovascular mortality,with a somewhat higher association for a maternal history[adjusted hazard ratio(aHR)=1.99,95%CI:1.36−2.92,P<0.001 for maternal history of premature CHD;aHR=1.52,95%CI:1.10−2.10,P=0.011 for paternal history of premature CHD].Family history of stroke or peripheral arterial disease did not predict cardiovascular *** history of premature CHD predicted cardiovascular mortality independently of baseline age(<60 years and≥60 years),hypertension,or hyperlipidemia and carried more important prognostic value in men rather than wo-m

关键词： cardiovascular Lipid mentioned

Randomized trial in malignant biliary obstruction:Plastic vs partially covered metal stents

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World Journal of Gastroenterology 2013年第46期19卷 8638-8646页

作者： Peter L Moses Khalid M AlNaamani Alan N Barkun Stuart R Gordon roger D Mitty M Stanley Branch Thomas E Kowalski Myriam Martel Viviane Adam Division of Gastroenterology and Hepatology University of Vermont Division of Gastroenterology McGill University Health Center McGill University Department of Epidemiology and Biostatistics and Occupational Health McGill University Health Center Division of Gastroenterology and Hepatology Dartmouth Hitchcock Medical Center Lebanon Division of Gastroenterology Tufts University School of Medicine Boston Division of Gastroenterology Duke University Medical Center Durham Division of Gastroenterology and Hepatology Thomas Jefferson University Hospital

AIM:To compare efficacy and complications of par-tially covered self-expandable metal stent(pcSEMS)to plastic stent(PS)in patients treated for malignant,infrahilar biliary ***:Multicenter prospective randomized clinical trial with treatment allocation to a pcWallstent(SEMS)or a 10 French *** patients aged≥18,for infrahilar malignant biliary obstruction and a Karnofsky performance scale index>60%from 6 participating North American university *** endpoint was time to stent failure,with secondary outcomes of death,adverse events,Karnofsky performance score and short-form-36 scale administered on a three-monthly basis for up to 2 *** analyses were performed for stent failure and death,with cox proportional hazards regression models to determine significant predictive ***:Eighty-five patients were accrued over 37mo,42 were randomized to the SEMS group and 83patients were available for *** to stent failure was 385.3±52.5 d in the SEMS and 153.3±19.8 d in the PS group,P=*** to death did not differ between groups(192.3±23.4 d for SEMS vs211.5±28.0 d for PS,P=0.70).The only significant predictor was treatment allocation,relating to the time to stent failure(P=0.01).Amongst other measured outcomes,only cholangitis differed,being more common in the PS group(4.9%vs 24.5%,P=0.029).The small number of patients in follow-up limits longitudinal assessments of performance and quality of *** an initially planned 120 patients,only 85 patients were ***:Partially covered SEMS result in a longer duration till stent failure without increased complication rates,yet without accompanying measurable benefits in survival,performance,or quality of life.

关键词： Randomized Biliary Obstruction Stent Plastic Metal Palliative Common bile duct

环氧酶2抑制剂的疗效与安全性新的研究结果令人鼓舞,但其危险效益比仍不清楚

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英国医学杂志中文版 2003年第3期6卷 133-134页

作者： roger Jones 邓瑞雪 Wolfson professor of general practice. Department of General Practice and Primary Care Guy's King's and St Thomas's School of Medicine London SE11 6SP

非甾体类抗炎药(NSAIDs)能够减轻机械性和炎症性关节病患者的疼痛并改善功能,同时也对其他很多疾病有效。但这些效果也付出了一定代价。在英国,每年大约有2000人死于由NSAIDs引起的上消化道病变,而且这类药物还对低位肠道、肺。

关键词：环氧酶2抑制剂疗效安全性非甾体类抗炎药罗非昔布

Hepatocellular carcinoma in Lebanon: Etiology and prognostic factors associated with short-term survival

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World Journal of Gastroenterology 2006年第22期12卷 3575-3580页

作者： César Yaghi Ala I Sharara Paul Rassam Rami Moucari Khalil Honein Joseph BouJaoude Rita Slim roger Noun Heitham Abdul-Baki Mohamad Khalifeh Sami Ramia Raymond Sayegh Service de Gastroenterologie Hotel Dieu de France University Hospital BeirutLebanon Service de Gastroenterologie Hotel Dieu de France University Hospital.Beirut.Lebanon Departments of Internal Medicine and Surgery American University of Beirut Medical CenterBeirutLebanon Service de Gastroenterologie Hotel Dieu de France University Hospital BeirutLebanon Service de GastroenterologieHopital Saint GeorgesBeirutLebanon Departments of Internal Medicine and Surgery American University of Beirut Medical Center BeirutLebanon

AIM： To study the epidemiology of HCC in Lebanon and prognostic factors predictive of early mortality. METHODS： An observational follow-up cohort study of HCC cases diagnosed over a five-year period was carried out. Multivariate analysis was conducted to identify prognostic factors in comparison to Cancer of the Liver italian Program （CUP） score. Multiple variables including the etiology of underlying liver disease, the demographic characteristics of patients, and the severity of liver disease evaluated by the Child-Pugh score were studied. Tumor parameters included the time of diagnosis of HCC, alpha-fetoprotein level, number and size of nodules, presence of portal vein thrombosis, and treatment modalities. Death or loss of follow-up was considered as an end-point event. RESULTS： Ninety-two patients （mean 60.5 ± 22.3 years） were included. Etiology of underlying disease was hepatitis B, C, and alcohol in 67%, 20%, and 23.5% respectively. Child-Pugh class at diagnosis was A, B, and C in 34.8%, 39.3% and 25.8% respectively. Overall survival was 44.8%, 32.8% and 17.6% at 1, 2 and 3 years respectively （mean F/U 40.2 ± 23.5 mo）. Multivariate analysis identified three predictors of early mortality （〈 6 mo）： bilirubin 〉 3.2 mg/dL （P 〈 0.01）, HCC as first presentation of liver disease （P = 0.035）, and creatinine 〉 1 mg/dL （P = 0.017）. A score based on these variables outperformed the CLIP score by cox proportional hazard. ROC curve showed both models to be equivalent and moderately accurate.CONCLUSION： HBV is the leading cause of HCC in Lebanon. Independent predictors of early mortality are elevated bilirubin, creatinine and HCC as first manifestation of disease. Prospective validation of a score based on these clinical parameters in predicting short-term survival is needed.

关键词： Liver Epidemiology Hepatitis Neoplasm Cancer Cirrhosis